Marrow engraftment of hematopoietic stem and progenitor cells is independent of Galphai-coupled chemokine receptors
| Autor: | Gerald J. Spangrude, Anne Wiesmann |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Myeloid Stem cell factor Biology GTP-Binding Protein alpha Subunits Gi-Go Chemokine receptor Mice Genetics medicine Animals Virulence Factors Bordetella Progenitor cell Molecular Biology Cells Cultured Bone Marrow Transplantation Cell Biology Hematology Hematopoietic Stem Cells Transplantation Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure Phenotype Pertussis Toxin Immunology Cancer research Receptors Chemokine Bone marrow Cell Division Spleen Homing (hematopoietic) |
| Zdroj: | Experimental hematology. 27(5) |
| ISSN: | 0301-472X |
| Popis: | The mechanism of hematopoietic stem and progenitor cell (HSPC) homing to hematopoietic organs after transplantation is still poorly understood. There is evidence that HSPC homing is a multistep process involving integrins and other adhesion molecules as well as stimulation of cytokine and chemokine receptors, similar to the process of lymphocyte recirculation and leukocyte emigration. This study examined the effect of pertussis toxin (PT), an inhibitor of signaling by many G α i protein-coupled chemokine receptors, on engraftment of HSPC. An in vitro incubation of total bone marrow cells in PT-supplemented media prior to transplantation into lethally irradiated syngeneic mice resulted in an increase in marrow repopulation and a parallel decrease of colony-forming unit-spleen (CFU-S) on day 13. PT treatment of Rh low Lineage neg Sca-1 pos cells prior to transplant resulted in delayed spleen cell engraftment, but no observable difference in the bone marrow cellularity compared to animals transplanted with untreated cells. FACS analysis of hematopoietic organs revealed that myeloid cell recovery in the bone marrow was unaffected by PT treatment of HSPC. However, a reduced myeloid cell recovery in the spleen and an increased B lymphoid recovery in both the spleen and the bone marrow were observed in recipients of PT-treated grafts relative to untreated grafts. To test the hypothesis that PT inhibits proliferation rather than engraftment of HSPC in the spleen, the effect of PT on cytokine-stimulated proliferation of HSPC was tested. Although an inhibition of the growth of microcolonies in response to interleukin 6 as a single cytokine could be observed after PT treatment, colony growth of HSPC after steel factor or steel factor + interleukin 6 stimulation was unaffected by PT. This study demonstrates that bone marrow, but not splenic, recovery after HSPC transplantation is independent of PT-sensitive mechanisms. It is likely that PT inhibits spleen cell recovery by disrupting a Gα i -coupled homing receptor expressed by HSPC. These studies support the hypothesis that distinct mechanisms regulate splenic vs bone marrow engraftment of HSPC, and that B lymphocyte progenitors and HSPC can utilize a PT-resistant homing mechanism to localize in hematopoietic tissues after transplantation. |
| Databáze: | OpenAIRE |
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